Chromosome disorders
Lecture Details Melanie Pritchard; Week 4 MED1011; Biochemistry Lecture Content Humans have 46 chromosomes in 23 pairs; karyotype is photomicrograph of chromosomes arranged according to set classification. It is usually studied in peripheral lymphocytes but amniotic fluid or cells from CVS can be used. It is done by extraction of lymphocyte culture, phytohaemagglutinin is added which stimulates T lymphocytes to divide, colchicine added after 48-72 hours to arrest cells at metaphase, cells fixed and placed on the slide. May be stained with a variety of stains, Giemsa is common (G-banding). Light bands contain most active genes, deletions and insertions of >4Mb of DNA can be identified. There are 22 pairs of autosomes from largest to smallest and one pair of sex chromosomes. Y chromosome is small and of paternal origin. Centromeres can be metacentric (near the middle of the chromosome), acrocentric (near one end) or submetacentric (between a middle and an end). Each chromosome has a long and a short arm. Long arm is q, short arm is p. Tip of each is the telomere. Ideogram is standard numbering system for G banding, used to describe location of genes. Karyotype is described with total number of chromosomes, sex chromosome makeup, description of any abnormality: 47, XX +21 - female Down syndrome. p short arm, q long arm, pter is tip of short arm, cen is centromere, del is deletion, ins insertion, inv inversion, pat paternal origin and mat maternal origin. Chromosome abnormalities are structural or numerical. Aneuploidy is missing or additional chromosomes. Monosomy is loss of a single chromosome, usually fatal before term. Trisomy is gain of one chromosome, tetrasomy is gain of 2. Polyploidy is multiple of chromosome number (2n). Most common polyploidy is triploidy. Polyploidy can be from two sperm or diploid sperm, diploid egg is not viable. Megakaryocytes are polyploid naturally (8-16n). Aneuploidy is usually due to non-disjunction at anaphase. If it arises during mitosis it can cause mosaicism. : Edwards is tri18, Patau tri13, Down tri21. Edwards and Patau usually fatal during first few weeks of life. Chromosome 21 is gene poor and is smallest autosome. In Edwards and Patau only 10% survive past first few weeks. Maternal age is linked to all syndromes. 60% of trisomy 21 aborts spontaneously. The extra 21 is usually maternal in origin (age). Sex chromosome aneuploidy can be Kleinfelters (47 XXY), Turners (45, X). Kleinfelters is sterile and has mild learning defects. Turner's syndrome is characterised by peripheral lymphoedema and redundant neck skin, may present with primary amenorrhoea or short stature- most only have maternal X chromosome. Balanced rearrangement is where there is no net loss or gain of chromosomal material, usually harmless unless break point interferes with a functional gene. Unbalanced is usually severe. 2 breaks in a chromosome can result in inversions or interstitial deletions. Breaks in one or more chromosomes can result in reciprocal translocation, Robertsonian translocation, insertional translocation. Reciprocal translocation is balanced. Robertsonian translocations have two short arms (only occurs in acrocentric pairs) break off and long arms join. 14-21 translocation is common here and can cause trisomy 21 (5%). Insertional translocations involve a deletion in one chromsome and insertion into another. Readings Life (9th), 223-229=